Pathology Flashcards
Physical Alterations for Adaptation
- Atrophy - cells become smaller due to disuse, malnourishment, de-nervation, vascular insufficiency, GI disease, nutrient deficiency, organ may decrease in size
- Hypertrophy - Increase in size as have to perform at a higher level than previously, organ may increase in size
- Hyperplasia - Increase in number of cells due to greater demand. Also leads to larger organ size.
- Metaplasia - substitution of normal mature cell type with another. Often less specialised cell of same lineagr, may be adaptive but often pathological
Non-adaptive Cell Alterations
- Dysplasia - change in cell structure, sometimes reversible
- Neoplasia - tissue undergone permanent DNA change and is passed on to cell prgeny, rarely reversible, if so different to original cell known as anaplasia
- Hamartoma - disorganized growht of tissue in a normal location, usually form embryonic cells that are stalled during development and then start proliferating again
- Choristoma - growht of normal tissue in abnormal location, embryonic cells switch on genes and cause it to differentiate into the wrong cell for the location
Histologic Changes of Necrotic Tissue
- Pyknosis - shrunken, homogenous, dark, round
- Karryohexis - fragmentation of chromatin
- Karyolysis - dissolution of chromatin
- Anuclear
- Increased eosinophilia, followed by dissolution
- loss of adherence to B and neighbouring cells
- rupture of cell membrane
Gross Appearance of Necrotic Tissue
- Coagulative necrosis - firm texture, denaturation of structural proteins and enzymes meaning no proteolysis, eosinophilic anucleate cells may persist for days, necrotic cells removed by phagocytosis
- Caesation Necrosis - cheese like white appearance of area of necrosis, microscopically a collection of fragmented/lysed cels and amophorus granular debris, distinctive inflammatory border, charecteristic of grnuloma
- Liquefecative necrosis - dead cells transformed into liquid, yellow dur to accumulation of leukocytes due to bacterial presence
- Gangrenous necrosis - not a specific pattern of death, usually applied to limb in lower leg where lost blood supply, if bacteria present see liquefecative
- Fat necrosis - Release of pancreatic lipases that split triglyceride esters contained within fat cells and combine with Ca2+ to give chalky white areas
Intracellular Accumulations in Degeneration
- Lipid accumulation
- Lipoprotein accumulation - dysfunctional enzymes cause accumulation of substrate, may be due to genetic defects, toxins damage enzymes, remains of incomplete digestion
- Glycogen accumulation - excessive in animals with abnormal glycogen or glucose metabolism eg diabetes
- Protein accumulation - reabsorption droplets in epithelial cells of renal proximal ubules or intestinal epithelium, may have accumulation of misfolded protiens
- Auto[hagic vacuoles - large inclusions, common in cells with sublethal damage and way to rid of damaged or senescent organelles
- Crystallin Protein inclusion bodies
- Viral and lead inclusion bodies - left over from viruses during replication and lead in lead poisoning
Extracellular Accumulations in Degeneration
- Amyloid accumulation - extracellular and compress adjacent parenchymal cells causing atrophy or death, may be systemic, localized or B-amyloids
- Fibrinoid changes - most often in vasculature as result of immunoglobulin, complement or plasma proteins, due injury to intima and media
- Gout - deposition of Na-urate crystals or urates in tissue
- Pseudogout - deposition of Ca-pyrophosphate crystals
- Cholestrol - by product of haemorrhage and necrosis, incites granulomatous response
- Pathologic calcification - common sites include necrotic myocardium, skeletal muscle, granulomas, dead parasites calcinosis is Ca2+ under skin, calcinosis cutis in dogs with hyper-adrenocorticosism from increased corticosteroids. Calcinosis circumscripta in german shephards and great danes, also in areas of repeated trauma. Metastatic calcification is secondary to hypercalcemia where large amounts Ca2+ enter cell, precepitate on organelles, esp mitochondria. Caused by renal failure, vit D toxicosis, paprthhormone. Heterotopic bone - bone forming at abnormal site, heterotopic - microscopically normal but at abnormal location arising from embryological resets and osseous metaplasia where there is differentiation into osteoblasts.
- Exogenous pigment - e.g. carbon from inhalation, tattoos, dust, caretenoid, tetracycline antibiotics causing brown teeth/bones. Most pigmentation seen in fat stores
- Endogenous pigment - Melanin (normally produced) but may have hyper-pigmentation in chronic injury, endocrinopathies, melanoma etc, lipofuscin wear and tear age pigment that accumulates in time-dependent manner in post mitotic cells and final breakdown product is non-deleterious. Ceroid chemically similar but accumulates in response to malnutrition, vit E deficiency, cachexia of cancer, irridation and is deleterious to cells
- Haematogenous pigments
Haematogenous Pigments
- Cyanosis - cyanide binds to cytochrome oxidase, no oxidative phosphorylation and paralysis of cellular respirtion leading to bright red venous blood, CO poisoning leads to formation of carboxyhemaglobin
- Methaemoglobin - oxide of haemoglobin and ferrous ion of haemoglobin converted to ferric ion, a reddish brown colouration of blood and tissues, poisoning by nitrates, ingestion of acetaminophen, mapthalene, local anaesthic
- Intravascular haemolysis - haemoglobin released and excreted form kidney, staining tissue dark red to black
- Formalin pigment
- Parasite hematin - parasite metabolism of haemoglobin
- Haemosiderin - Formed from aggregates of ferritin due to excess iron in erythocyte breakdown, mainly in spleen
- Bilirubin - low levels normally present due to erythrocyte breakdown, left over from breakdown of porphyrin-ring after iron removal
- Icterus - Jaundice by bilirubin due to excess production or reduced clearance. May be increased production in haemolytic diseases, hematomas or reduced uptake by hepatocytes because they are impaired
- Poryphyria - inherited metabolic defect in heme synthesis causd by deficiency of uroporphyrinogen III cosynthetase. Bones and teeth fluoresce red under UV
Differences Between Apoptosis and Necrosis
CTL Mediated Apoptosis
For virus infected cells.
Upon entry of granzyme B, through perforin channels, it cleaves and activates BID , translocates to mitochondria, opens pores (Bax/Bak channels) within the mitochondral outer membrane
Cytochrome C is release from the intermediate space into cytoplasm acts as co-factor for assembly of a caspase-9 activating complex
The apoptosome promotes activation of downstream caspases
These again coordinate apoptosis through restricted proteolysis of, 100 of substrate proteins
Granzyme A cleaves a protein within an ER-associated protein complex (SET complex) -> allows translocation of nuclease to nucleus -> catalyses single- strand DNA breaks
Mechanisms of Apoptosis
Role of p53
Effects of Dysregulated Apoptosis
Defective, increased cell survival - neoplasia, autoimmunity, developmental defects
Increases, decreased cell survival - Neurodegenerative disease, ischaemic injury, death of virus infected cells, developmental defects
Consequences of ATP Depletion
- ER swelling, cellular swelling, loss of microvilli blebs
- Clumping of nuclear chromatin
- Decreased protein synthesis, lipid deposition
Consequences of Over-Production of ROS
Lipid peroxidation of membranes by double bonds of unsaturated fatty acids which are attacked causing severe membrane damage, oxidative modification or proteins resulting in protein crosslinke and protein fragmentation and oxidative or nitrative modifications of DNA resulting in DNA mutations.
Role of Teleomeres
Contain repeated bases, repeated 500-5000 times at linear ends of choromosomes, ensures replication of chromosomal ends, protecting chromosomal terminifrom fusion and degredation. Teleomerase is a specialised RNA-protein complex that uses its own RNA as a template for adding nucleotides to the ends of chromosomes and is repressed by regulatory proteins, High activity in germ cells, lower in stem cells and undectable in somatic tissues.
